Methods and devices for COVID-19 testing using urine samples

ABSTRACT

The present invention generally includes methods, devices and/or kits for the detection of a COVID-19 infection in an individual by measuring the level or concentration or one or more ions present in a urine sample that is substantially free of COVID-19 RNA, antibodies, or antigen material.

This application is a continuation application that claims priority toU.S. Non-Provisional application Ser. No. 17/681,839 filed on Feb. 27,2022, which claims priority to U.S. Provisional Application No.63/154,805, filed on Feb. 28, 2021, each of which are incorporatedherein in their entirety.

BACKGROUND

The present invention generally relates to detecting COVID-19infections. More specifically, the present invention relates toanalyzing one or more urine samples to detect the onset of a COVID-19infection without having to use SARS-CoV-2 virus, or viral material,and/or antibodies produced in response to a COVID-19 infection. Thepresent invention further includes methods of detecting and/ordiagnosing COVID-19 infection by measuring and/or quantifying changes tomineral or ionic levels in a urine sample. Furthermore, the presentinvention includes devices, test strips, test materials, and/or kitsuseful in the detection of at least one mineral and/or ionic level in aurine sample.

Coronavirus disease 2019, hereinafter referred to as “COVID-19”, is aviral contagious disease caused by severe acute respiratory syndromecoronavirus 2 hereinafter referred to as “SARS-CoV-2”. Symptoms ofCOVID-19 are variable and may begin one to fourteen days after exposureto the virus. Around one in five infected individuals do not develop anysymptoms, while other individuals can also spread the virus as early astwo days before manifestation of any symptom. In general, people remaininfectious for up to ten days in moderate cases, and around two weeks insevere cases.

Various testing methods have been developed to diagnose a COVID-19infection even before the onset of symptoms. Standard methods includereal-time reverse transcription polymerase chain reaction, antigen, andblood tests. Samples can be obtained by various methods, including anasopharyngeal swab, sputum (coughed up material), throat swabs, deepairway material collected via suction catheter or saliva with the goalat detecting the presence of viral RNA fragments. Results are generallyavailable within a few hours to several weeks although delays have beenreported due to overwhelming demand for testing, lack of test reagents,etc. Spit tests are deemed easier than using swabs, which allows forat-home testing even though saliva generally has less RNA materialneeded for effective detection. Sensitivity from molecular testingtypically ranges from 68% to 100%, while the specificity ranges from 92%to 100%. Antigen test sensitivity and specificity are typically lowerthan molecular techniques. In all cases, test performance data in bothasymptomatic and symptomatic persons are limited.

People without symptoms can pass on SARS-CoV-2 but estimating theircontribution to outbreaks is challenging due in part to the inability todistinguish between people who are asymptomatic and pre-symptomatic.

SUMMARY OF THE INVENTION

The present invention generally includes methods, strips, materials,devices, probes, and/or kits for the detection of a COVID-19 infectionin an individual by measuring the level or concentration or one or moreions present in a urine sample without having to use RNA, one or moreantibodies, or one or more antigen material.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is TABLE 1A: NORMAL URINARY ION VALUES: DAYS 1 TO DAY 15

FIG. 2 is TABLE 1B: NORMAL URINARY ION VALUES: DAY 16 TO 31

FIG. 3 is TABLE 1—COVID 19 INFECTION OR ILLNESS URINARY ION VALUES

FIG. 4 is TABLE 3: EXAMPLE DATASET USED TO TRAIN MACHINE LEARNING ANDDEEP LEARNING MODEL TO PREDICT COVID-19 STATUS

DETAILED DESCRIPTION

As used herein, the term “asymptomatic” refers to an infected individualwho never develops and/or demonstrates COVID-19 symptoms throughout thecourse of a COVID-19 infection or illness.

As used herein, the term “pre-symptomatic” refers to an infectedindividual who develops and/or demonstrates mild symptoms beforedeveloping and/or demonstrating more severe symptoms. Furthermore, theterm “pre-symptomatic” as used herein generally refers to an infectedindividual who initially does not develop and/or demonstrate COVID-19symptoms but goes on to develop and/or demonstrate COVID-19 symptomsafter a period of time.

As used herein, the term “antigen” refers to a part of a pathogen thatelicits an immune response.

As used herein, the term “antibody” generally refers to a large,Y-shaped protein used by an immune system to identify and neutralize oneor more foreign object(s), such as one or more pathogenic bacteria andvirus(es). Furthermore, the term “antibody” as used herein refers to oneor more proteins that help fight off one or more infections and canprovide protection against getting the infection again. Additionally,the term “antibody” as used herein generally refers to one or moreimmunoglobulin(s) (Ig) used by an immune system to identify andneutralize one or more foreign object(s) that gain access to a body.

As used herein, the term “colorimetric analysis” refers to a method ofdetermining a concentration of an element, an ion, a chemical, acompound, a chemical element, chemical compound, or any combinationthereof, in a solution with the aid of a color reagent. Furthermore, theterm “colorimetric analysis” as used herein may also refer to atechnique used to determine a concentration of one or more coloredelements, ions, chemical elements, chemical compounds, compound(s), orany combination thereof, in a solution, mixture, or suspension.Additionally, the terms “colorimetry” and “colorimetric analysis” willbe used interchangeably throughout the present invention.

As used herein, the term “sensitivity” refers to an ability of a test tocorrectly identify and/or classify one or more individual(s) with adisease. Additionally, the term “sensitivity” is meant to encompass howoften a test can correctly generate a positive result for one or moreindividual(s) who have the condition that is being tested for inaccordance with the present invention. Furthermore, the term“sensitivity” encompasses a percentage or proportion of samples thathave a condition. In an example, a test with a 90% sensitivity willcorrectly return a positive result or classification for 90% of thetested population who have a disease and will return a negative resultfor 10% of the tested population who have the disease and should havetested positive.

As used herein, the term “true positive rate” refers to a proportion ofone or more individual(s) with a known positive condition for which atest result for the one or more individual(s) is positive.

As used herein, the term “true negative rate” refers to a proportion ofone or more individual(s) with a known negative condition for which thetest result for the one or more individual(s) is negative.

As used herein, the term “specificity refers to an efficacy and/oreffectiveness of a test to correctly identify or classify or confer anegative status to one or more tested individual(s) who do not have thecondition being tested. For example, a test with a 90% specificity willcorrectly return a negative result for 90% of the tested population whodo not have the condition for which the population is being tested andwill return a positive result for 10% of the tested population who donot have the disease and should have tested negative.

As used herein, the term “selectivity of a reaction” generally refers toa ratio of an amount of desired product formed (typically in moles) toan amount of an undesired product formed (typically in moles).

As used herein, the term “machine learning sensitivity” generally refersto the proportion of actual positive cases that are correctly predictedby a machine learning algorithm and/or model. In addition, the term“machine learning sensitivity” as used herein generally refers to ametric that evaluates an ability of a machine learning model oralgorithm to correctly predict true positives of each availablecategory. Furthermore, the term “machine learning sensitivity” is meantto encompass a proportion of actual positive cases that are predicted aspositive (or true positive) in the present invention. In one example,“machine learning sensitivity” measures the proportion or probability ofactual positive cases that got predicted correctly by a machine learningmodel or algorithm.

As used herein, the term “machine learning specificity” generally refersto a proportion of actual negative cases that were correctly predictedby a machine learning algorithm or model. In addition, the term “machinelearning specificity” generally refers to a metric that is effective toevaluate a machine learning model or algorithm's ability to correctlypredict true negatives of each available category. Furthermore, the term“machine learning specificity” typically characterizes a proportion ofactual negatives that were correctly predicted as negative (or truenegative) in the present invention. For example, the “machine learningspecificity” measures the proportion or probability of actual negativecases that were predicted correctly by a machine learning algorithm ormodel.

As used herein, the term “accuracy” generally refers to the numericalproportion or probability of a true positive result or status no matterif the result or status is positive or negative within a selectedpopulation.

As used herein, the term “false positive” generally refers to an errorin a binary classification in which a test result incorrectly indicatesthe presence of a condition, such as a disease when the condition (ordisease) is not present. Furthermore, the term “false positive” as usedherein generally refers to a result that indicates a given conditionexists when the given condition does not. In addition, the term “falsepositive” may be used interchangeably with the term “false positiveerror” in the present invention.

As used herein, the term “false negative” generally refers to an errorin a binary classification in which a test incorrectly fails to indicatethe presence of a condition, such as a disease when the condition (ordisease) is present. Furthermore, the term “false negative” as usedherein, generally refers to a test result which wrongly indicates that acondition does not exist then the condition is present. In addition, theterm “false negative” may be used interchangeably with the term “falsenegative error” in the present invention.

As used herein, the term “hypokalemia” generally refers to a low levelor concentration of potassium in the blood serum of a person or anindividual and can be measured by a blood potassium test or a serumpotassium test. By “low” is meant potassium concentrations or levelsgenerally less than about or below about 3.5 millimoles (“mmol”)/Liter(“L”), less than about 3.0 mmol/L, and/or less than about 2.5 mmol/L inthe present invention. Furthermore, the term “hypokalemia” is meant toencompass a decrease in blood serum potassium concentration or level toa value that is below the normal range of serum potassium levels, suchas less than about 3.5 milliequivalents per liter (mEq/L), less thanabout 3.0 mEq/L, less than about 2.5 mEq/L, and/or less than about 2.0mEq/L in the present invention.

As used herein, the term “hyperkalemia” generally refers to a high levelor concentration of potassium in the blood serum of a person orindividual and can be measured by a blood potassium test or a serumpotassium test. By “high” is meant potassium levels or concentrationsgenerally more than about 5.0 mmol/L (or 5 mEq/L), more than about 5.1mmol/L (or 5.1 mEq/L), and/or more than about 5.2 mmol/L (or about 5.2mEq/L) of blood serum in the present invention. Furthermore, the term“hyperkalemia” is meant to encompass an increase in serum potassiumlevel or concentration to more than the normal blood serum potassiumlevels, such as to more than about 5.0 mEq/L (or 5.0 mmol/L), more thanabout 5.1 mEq/L (or 5.1 mmol/L), more than about 5.2 Eq/L (or 5.2mmol/L), and/or more than about 5.3 mEq/L (or 5.3 mmol/L).

As used herein, the term “hyponatremia” generally refers to a low levelor concentration of sodium in the blood serum of a person or individualand can be measured by a sodium blood test or a serum sodium test. By“low” is meant blood sodium concentrations or levels of less than about140 mEq/L (or about 140 mmol/L), less than about 136 mEq/L (or about 136mmol/L), less than about 135 mEq/L (or about 135 mmol/L), and/or lessthan about 130 mEq/L (or about 130 mmol/L). Furthermore, the term“hyponatremia” is meant to encompass a decrease in serum sodiumconcentration to less than about 136 mEq/L (or about 136 mmol/L), lessthan about 135 mEq/L (or about 135 mmol/L), less than about 130 mmol/L(or about 130 mEq/L), and/or less than about 125 mEq/L (or about 125mmol/L).

As used herein, the term “hypernatremia” generally refers to a serumsodium concentration of more than about 145 mEq/L (or about 145 mmol/L),more than about 146 mEq/L (or about 146 mmol/L), more than about 147mEq/L (or about 147 mmol/L), and/or more than about 150 mEq/L (or about150 mmol/L). Furthermore, the term “hypernatremia” is meant to encompassan increase in sodium level or concentration in blood to more than about145 mEq/L (or 145 mmol/L), more than about 146 mEq/L (or 146 mmol/L),more than about 147 mEq/L (or 147 mmol/L), and/or more than about 150mEq/L (or 150 mmol/L) in the present invention.

As used herein, the term “hypercalcemia” generally refers to a totalblood calcium level in blood serum that is greater than a normal totalblood calcium level range of about 2.1 to about 2.6 mmol/L (or about 8.5to about 10.7 milligrams per deciliter (mg/dL)), or about 4.3 to about5.2 mEq/L). For example, a total blood serum calcium level orconcentration of more than about 2.6 mmol/L (or about 5.2 mEq/L) isgenerally characterized as hypercalcemia as the normal total bloodcalcium level range is about 2.1 to about 2.6 mmol/L in an adult. Inanother example, the total blood calcium is more than about 10.7 mg/dL,more than about 10.8, and/or more than about 10.9 mg/dL. In anotherexample, an ionized calcium concentration or level of more than about5.4 mg/dL, more than about 5.5 mg/dL, more than about 5.6 mg/dL, and/ormore than about 5.7 mg/dL indicates hypercalcemia. In another example, adiagnosis of hypercalcemia occurred when the ionized calcium was morethan about 1.30 mmol/L. Furthermore, the term “hypercalcemia” is meantto encompass an increase in total blood serum calcium level orconcentration to above the normal range for total blood calcium level tomore than about 2.65 mmol/L (or 5.3 mEq/L), more than about 2.7 mmol/L(or 5.4 mEq/L), more than about 2.75 mmol/L (or 5.5 mEq/L), more thanabout 2.8 mmol/L (or 5.6 mEq/L).

As used herein, the term “hypocalcemia” generally refers to a totalserum calcium concentration of less than about 8.8 mg/dL (or less thanabout 2.20 mmol/L), less than about 8.7 mg/dL, less than about 8.6 mg/dLand/or less than about 8.5 mg/dL in the presence of a normal plasmaprotein concentration. In addition, the term “hypocalcemia” is meant toinclude a serum ionized calcium concentration of less than about 4.7mg/dL (or less than about 1.15 mmol/L), less than about 4.6 mg/dL, lessthan about 4.5 mg/dL, or less than about 4.4 mg/dL. Furthermore, theterm “hypocalcemia” is meant to encompass a decrease in total bloodserum calcium level or concentration to below the normal range for totalblood calcium level of less than about 2.20 mmol/L, less than about 2.1mmol/L, less than about 2.0 mmol/L, less than about 1.9 mmol/L in thepresence of normal plasma protein concentrations.

As used herein, the term “total calcium test” generally refers tomeasurement or quantification of both free ionized calcium and boundcalcium, such as for example calcium bound to protein in a sample.

As used herein, the term “ionized calcium test” generally refers tomeasurement or quantification of only free calcium in a sample.

As used herein, the term “hypermagnesemia” refers to a high level ofmagnesium in blood serum. In general, normal blood magnesium levels isabout 1.3 to about 2.1 mEq/L or 0.65-1.05 mmol/L (SI units) in an adult,about 1.4 to about 1.7 mEq/L in children, or about 1.4 to about 2 mEq/Lin newborn children. As such, hypermagnesemia is indicated when blood(serum) levels of magnesium exceed 3 mEq per liter with variationsoccurring due to reporting from different laboratories. For example,hypermagnesemia is diagnosed when concentrations of magnesium aregreater than about 1.1 mmol/L in blood serum are reported.

As used herein, the term “hypomagnesemia” generally refers to when bloodlevels of magnesium drop to or are below about 0.5 mEq per liter and canbe measured by blood magnesium or serum magnesium test with variationsoccurring due to reporting from different laboratories. While notwanting to be bound to theory, it is to be understood that a normal lossof magnesium ions in urine is about 51 to about 269 mg per day based ona 24-hour collection for individuals between about 18 and about 83 yearsof age. In one example, urinary magnesium levels of more than about 24mg/day based on a 24-hour collection may indicate a hypomagnesemiastatus. In another example, hypomagnesemia status is indicated due tolosing more than about 50 mg magnesium per 24-hour timeframe in urine.In a third example, a status of hypomagnesemia is indicated by a 24-hoururine magnesium of more than about 24 mg/day or fractional excretion ofmore than about 0.5% based on 24-hour urine collections.

As used herein, the term “serum” generally refers to the fluid or liquidthat remains after blood has clotted.

As used herein, the term “plasma” generally refers to the liquid orfluid that remains when clotting is prevented with the addition of ananticoagulant.

As used herein, the term “interlaboratory variation” generally refers todifferent laboratories performing the same assay and obtainingstatistically different results on the same sample.

In addition, it is to be understood that reference ranges for serumand/or total blood mineral, ion, or any combination thereofconcentrations or levels will vary by age and sex and laboratory whenpracticing the present invention.

As used herein, the term “urine output” or “urine volume excreted” isthe volume of urine produced by a human body in a day and may beassessed with the amount of urine produced over a 24-hour timeframe. Ingeneral, the normal range of urine output is about 500 to about 2,000milliliters per day based on a normal fluid intake of about 2 liters perday. However, different laboratories may use report or use slightlydifferent values. Other examples of urine output include more than about0.5 mL per kg body weight per hour for an adult; more than about 1 mlper kg body weight per hour for a child; and more than about 2 mL per kgbody weight per hour for a neonate or baby that is less than about 1year old.

As used herein, the term ‘hypercalciuria’ generally refers urinaryexcretion of more than about 20 to about 250 mg of calcium per day inwomen, more than about 20 to about 275 mg of calcium per day in men, ormore than about 4 mg per kg body weight per day while consuming aregular unrestricted diet. Furthermore, the term “hypercalciuria” ismeant to include any level of urine calcium that exceeds net intestinalabsorption in a human that leads to a net loss of calcium whenpracticing the present invention. For example, a urinary excretion ofmore than about 200 mg of calcium per liter in a urine sample isbelieved to indicate hypercalciuria. In addition, the term“hypercalciuria” as used herein in meant to include excess calcium inurine in the present invention as demonstrated by having more than about220 to about 2100 mg calcium per g creatinine. In another example,hypercalciuria is indicated when more than about 350 mg of calcium isexcreted over a 24-hour time frame by a human.

As used herein, the term “hypocalciuria” generally refers to a low levelof calcium in the urine. By “low” is meant about 50 to about 150 mg/dayof calcium in urine (from a diet that is low in calcium) as measured byurinalysis (calcium) or Urinary Ca+2. In general, normal volumes ofurine collected over a 24-hour period typically includes about 100 (15mmol) to about 250 (20 mmol) mg calcium. When a diet is low in calciumconsumption, normal urine volumes collected over a 24-hour time periodgenerally includes about 50 to about 150 mg calcium and may drop toabout 5 to about 40 mg calcium. As the present invention includes spoturine analysis, calcium may also be reported out as mg calcium per gramcreatinine as this metric is not affected by urine volume.

As used herein, the term “low urinary chloride” generally refers to alow level of chloride in the urine. Typically, the normal range ofchloride in urine is about 110 to about 250 mEq per day for a 24-hoururine collection although other ranges have been reported. For example,normal values for urinary chloride ranges from about 140 to about 250mEq/L for a 24-hour urine sample. In another example, a random sample ofurine includes normal ranges from about 20 to about 40 mEq/L (or about20 to about 40 mmol/L) urinary chloride when measuring urinary chloridelevels. in an example, the term “low urinary chloride” is meant toinclude less than about 20 millimoles per liter or milliequivalents perliter urine with some labs varying in their definition of a normal rangewhen using a urine chloride test. Results may be given inmilliequivalents per liter (mEq/L) or millimoles per liter (mmol/L).

As used herein, the term “high urinary (or urine) chloride” is meanturine chloride levels of more than the normal range of about 110 toabout 250 mEq per day for a 24-hour urine collection. In one example, alevel of about 40 mEq/L (40 mmol/L) indicates “high urinary chloride”levels. In another example, “high urinary chloride” generally containsmore than a normal range of about 140 to about 250 mEq/L for a 24-hoururine sample. In another example, “high urinary chloride” refers to anamount greater than 140 mEq/L urine over a 24 hour urine collection.

As used herein, the term “high urinary (or urine) sodium” is meant urinesodium levels of more than about 40 mEq/L (40 mmol/L) indicates highurinary sodium levels. In another example, urinary sodium levels areconsidered high when values are more than about 100, about 150, about200 or about 220 mEq/L.

As used herein, the term “low urinary sodium” generally refers to lessthan about 20 mEq/L in a urine sample when measured in a one-time urinesample with variations occurring due to reporting from differentlaboratories. Typically, a normal urine sodium value is about 20 mEq/Land can generally range from about 40 to about 220 mEq/L per day (orabout 40 to about 220 mmol per day) for a urine sample collected over a24-hour time period depending on the dietary salt intake. Other examplesof low urinary sodium values range are generally less than about 40mEq/L. In general, urine samples are normally collected over a 24-hourtime period.

As used herein, the term “urinary potassium” refers to the presence ofpotassium ion in a volume of urine. In general, urinary potassiumexcretion is regulated by serum potassium concentration and may beassessed via a 24-hour urine potassium collection. In one example, aurinary potassium excretion of an individual with hypokalemia is loweredto less than about 25 mEq/day based on a 24-hour collection. In anotherexample, urinary potassium excretion to less than about 15 mEq/L basedon a 24-hour collection may indicate hypokalemic status in anindividual. In another example, urine potassium concentration exceeding40 mEq/L may also be observed in an individual with hypokalemia. Inanother example, potassium to creatinine ratio of less than about 1.5mEq potassium/mmol creatinine may be observed in an individual withhypokalemia. In another example, a potassium-to-creatinine ratio greaterthan about 20 mEq/g creatinine has been suggested to indicate thepresence of hypokalemia in an individual. Furthermore, one method ofpracticing the present invention of testing for urinary potassiumexcretion is to measure spot urine potassium in a morning sample due inpart to diurnal variations.

As used herein, the term “urinary pH” generally refers to a measure ofhow acidic or alkaline (basic) a volume of urine is.

As used herein, the term “creatine” generally refers to a breakdownproduct of creatine phosphate derived from muscle and proteinmetabolism. Creatinine can be removed from the blood chiefly by thekidneys and is released at a constant rate by the body depending in parton the muscle mass of an individual. In one example, urine values forcreatinine range from about 955 to 2,936 milligrams (mg) per 24-hourtime frame for males; and about 601 to about 1,689 mg per 24-hour timeframe for females, depending on age and amount of lean body mass of theindividual with variations occurring due to reporting from differentlaboratories. In another example, urine values for creatinine based on a24-hour time frame for urine collection range from about 500 to about2000 mg/day (or about 4,420 to about 17,680 mmol/day) depending on ageand amount of lean body mass. In a third example, urine values forcreatine range from about 14 to about 26 mg per kg of body mass per dayfor men (or about 123.8 to about 229.8 μmol/kg/day) and about 11 toabout 20 mg per kg of body mass per day for women (or about 97.2 toabout 176.8 μmol/kg/day). In a fourth example, urine values forcreatinine for males range from about 0.8 to about 1.8 g/day (or about 7to about 16 mmol/day), and urine values for females range from about 0.6to about 1.6 g/day (or about 5.3 to about 14 mmol/day). In a fifthexample, urine creatinine concentrations range from about 40 to about300 mg/dL in males; and about 37 to about 250 mg/dL in females.

As used herein, the term “specific gravity” of urine generally refers toratio of the density of urine to a density of a standard substance, suchas water. Furthermore, the specific gravity of urine refers to a ratioof the density of urine to the density of water at the same temperatureand pressure. In addition, the term “specific gravity is meant toencompass the ratio of the mass of a solution compared to the mass of anequal volume of water when practicing the present invention. Typically,the normal specific gravity of urine ranges from about 1.005 to about1.030 with variations occurring due to reporting from differentlaboratories. The terms “urine specific gravity” and “specific gravityof urine” are used interchangeably herein.

As used herein, the term “clean sample” or “clean catch sample”generally refers to a sample of urine that is substantially free ofblood, dirt, particulate, microparticulate, one or more COVID-19antigens, one or more COVID-19 antibodies, COVID-19 RNA material, feces,or the like. Furthermore, the term “dean sample” or “clean catch sample”is meant to encompass a urine sample in which germs from the penis orvagina are prevented from being present. In one example, a dean sampleof urine is obtained by filtering the urine sample through amicrofiltration membrane. In another example, a clean sample of urine isobtained by filtering a urine sample through an ultrafiltrationmembrane. In another example, a clean sample of urine is obtained byfiltering a urine sample through a nanofiltration membrane. In anotherexample, a clean sample of urine is obtained by removing suspendedsolids, bacteria, virus, blood, feces from a urine sample.

As used herein, the term “urine bicarbonate” or “bicarbonate in urine”generally refer to the concentration or level of bicarbonate in urineand is reported in millimolar for a specific pH.

As used herein, the term “urine osmolality” is used to measure thenumber of dissolved particles per unit of water in the urine. Ingeneral, normal urine osmolality after a 12 to 14-hour fluid restrictionis typically more than about 850 milliOsmality (mOsm)/kg water (SIunits). In another example, a random urine specimen has an osmolality ofabout 50 to about 1200 mOsm/kg water, depending on fluid intake (orabout 50 to about 1200 mmol/kg water (SI units)). In a third example, anindividual with a normal diet and normal fluid intake has a urineosmolality of approximately 500 to 850 mOsm/kg water. In a fourthexample, an osmolality of about 40 to about 80 mOsm/kg water has beenobserved as a minimal urine osmolality.

The present invention generally includes detecting, measuring and/ormonitoring one or more ions, one or more minerals, or any combinationthereof in a volume of urine to indicate the presence of a COVID-19infection or illness. More specifically, the present invention includesdetecting, measuring and/or monitoring changes over a specifiedtimeframe in the levels of one or more ions, one or more minerals, orany combination thereof, in a volume of urine. Exemplary ions orminerals of the present invention include one or more hydrogen,hydroxyl, sodium, potassium, chloride, calcium, magnesium ions, orcombination thereof. The present invention further includes measuringand/or monitoring body temperature levels and/or blood pressure valuesin an individual in combination with detecting, measuring, and/ormonitoring changes to urinary ionic levels or concentrations to indicatethe presence or absence of a COVID-19 infection or illness in anindividual. While not wanting to be bound to theory, it is to beunderstood that detecting, measuring, and/or monitoring of urine samplesof the present invention do not require the presence of any COVID-19antigen, COVID-19 antibody, or COVID-19 RNA material to indicate thepresence of a COVID-19 infection or illness.

In general, detection, measurement, and/or monitoring mineral and/orionic concentrations or levels are typically performed over a specifiedtimeframe when practicing the present invention. In an example, mineraland/or ionic levels are measured every 30 minutes. In another example,pH, urine mineral and/or ionic levels are measured every hour. Inanother example, urine pH, mineral and/or ionic concentrations areanalyzed every 24-hours. In another example, random or spot measurementof urinary pH, mineral and/or ionic levels is performed daily for aperiod of two weeks to about 30 days. In another example, urinary pH,minerals and/or ionic content is measured every two to three days.

Renin converts angiotensinogen to angiotensin I (“ANG I).Angiotensin-converting enzyme-1, hereinafter referred to as “ACE1” is animportant component of the renin-angiotensin system, hereinafterreferred to as the “RAS” that cleaves or converts ANG I into angiotensinII (“ANG II”). ANG II is responsible for inflammation and high bloodpressure. ANG II attaches or binds to angiotensin II type 1 receptor andworks to induce vasoconstriction, aldosterone secretion stimulation,hypokalemia, and pulmonary epithelium degradation.Angiotensin-converting enzyme-2, hereinafter referred to as “ACE2” isalso an important component of RAS that is generally found on thesurfaces of the lung, intestine, heart, GI tract and liver. ACE2 is usedto lower blood pressure by catalytically converting ANG II into a seriesof metabolites or into ANG 1-7 metabolites. By converting ANG II intoANG 1-7, ACE2 reduces ANG II levels as well as decreases the effect ofANG II since ANG II is degraded into ANG 1-7 metabolites that functionas vasodilators, which are known to modulate blood pressure. Therefore,RAS and/or the renin-angiotensin-aldosterone system (hereinafterreferred to as “RAAS”) regulates blood pressure, plasma potassium, fluidand electrolyte balance, and systemic vascular resistance in humansthrough ANG I and ANG II.

As noted above, SARS-CoV-2 is the virus that causes COVID-19 infectionor illness. ACE2 has been implicated in the etiology of SARS-CoV-2.While not wanting to be bound to theory, it is believed that “SARS-CoV-2virus” or “SARS-CoV-2” (used interchangeably herein) uses a receptor ofACE2 to penetrate a human host cell during the infection phase ofSARS-CoV-2. SARS-CoV-2 binding to ACE2 receptors leads to downregulationof ACE2 and/or an overall increase in ANG II. With the decrease in ACE2activity, less ANG II conversion to ANG 1-7 metabolites were observedwhich may result in greater cellular injury by ANG II. This might be whyACE2 receptors are believed to function as a COVID-19 “virus hook” or“cellular doorway” for the COVID-19 virus during infection in humans.Furthermore, as harmful ANG II effects are typically reduced by ACE2activity, COVID-19 virus binding to ACE2 receptors prevent ACE2 bindingand/or normal operation which may result in more ANG II-mediatedcellular injury.

ANG II typically increases aldosterone secretion, which is also known tomediate calcium, sodium, potassium, and other ionic levels in cells, andto modulate blood pressure. Therefore, it is believed SARS-CoV-2 mayimpair regulation of RAAS. As such, COVID-19 virus binding to ACE2receptor to enter and infect human cells may be considered a form ofRAAS dysregulation.

In healthy individuals, nearly all potassium filtered by the kidneys arereabsorbed to maintain optimal potassium levels. Typically, potassiumexcretion is stimulated by aldosterone and/or in response to dietaryintake of potassium to modulate optimal potassium levels. Higherprevalence of hypokalemia have been shown among severely ill patientswith COVID-19. In one example, clinical data among patients withCOVID-19 show a high proportion classified as having severe hypokalemia(blood plasma potassium of less than about 3 mmol/L) and hypokalemia(blood plasma potassium levels of about 3 to about 3.5 mmol/L).

It has been discovered that the onset of hypokalemia observed during aCOVID-19 infection may be detected by measuring and/or monitoringpotassium ion levels in urine in an individual, such as over a 1-day, ora 3-day period of time, or a 5-day period of time, or a 7-day period oftime, or a 10-day period of time, or a 14-day period of time, or a21-day period of time, a 31-day period of time or before, during andafter a COVID-19 infection. Hypokalemia in an individual may bedetected, measured, and/or monitored by observing urinary potassiumlevels of greater than normal urinary potassium levels, such as morethan 15 mEq/L (typically measured over a 24-hour timeframe). While notwanting to be bound to theory, it is believed that hypokalemia in anindividual results in the release of potassium into the urine.Typically, normal or reference values for urinary potassium levelsranges from about 25 to about 125 mEq/24-hr collection timeframe using aurine sample. A sudden increase in daily urinary potassium levels, suchas an increase of about 10%, about 15%, about 20%, about 30%, about 40%,or about 50% when compared to one or more prior measured, monitored,and/or detected urinary potassium levels may indicate the onset of aCOVID-19 infection. Similarly, urinary potassium levels orconcentrations of more than about 50 mEq, more than about 75 mEq, morethan about 80 mEq, more than about 85 mEq, more than about 90 mEq, morethan about 95 mEq, or more than about 125 mEq over a 24-hour collectionmay suggest COVID-19 virus binding. In an example, a spot urinepotassium sample having more than about 100 mEq/L to about 125 mEq/L maysuggest a COVID-19 infection.

In general, daily monitoring of urinary potassium levels will establishnormal urinary potassium levels prior to the onset of a COVID-19infection. While not wanting to be bound to theory, it is believedchanges from normal urinary potassium to higher urinary potassium levelsdue to blood potassium losses at the start of an COVID-19 infection maybe effective to indicate the start of a COVID-19 infection. Thus, anincrease in urinary potassium levels (or urine samples containing highlevels of potassium) when compared to prior measured, monitored and/ordetected urinary potassium values may correlate to the onset of aCOVID-19 infection.

Furthermore, while not wanting to be bound to theory, it is believedurinary potassium levels remain elevated for a period of time due to RASdysregulation and/or hypokalemia during a COVID-19 infection. This timeperiod may vary due to the severity of a COVID-19 infection or illness.In one example, urinary potassium levels remain about 10% higher, about20% higher, about 30% higher or about 50% higher than previouslymeasured, monitored and/or detected urinary potassium levels for atleast 72 hours. In another example, urinary potassium levels remainhigher than about 125 mEq per L for at least about 48 hours due to theonset or ongoing COVID infection. In a third example, urinary potassiumlevels remain higher than about 50, about 75, about 100 mEq/L for atleast about five days due to a COVID infection. Furthermore, once theCOVID-19 infection passes and the body normalizes (recovers or heals),it is believed urinary potassium levels drop to normal levels of about25 to about 125 mEq/day (or other normal urinary potassium range for anindividual) once hypokalemia is resolved and/or the COVID-19 infectiongoes away. Therefore, daily measurement of urinary potassium levels, ina fasted state for example, to detect abnormal increases in urinarypotassium is believed effective to detect the onset, duration andcompletion of a COVID-19 infection in healthy, symptomatic and/orasymptomatic individuals.

Sodium may also be filtered by the kidneys to maintain optimal sodiumlevels in healthy individuals. It has been discovered that the onset ofa COVID-19 infection may also be detected by measuring and/o monitoringurinary sodium levels in an individual over an extended period of time,such as over a 1-day, or a 3-day period of time, or a 5-day period oftime, or a 7-day period of time, or a 10-day period of time, or a 14-dayperiod of time, or a 21-day period of time, a 31-day period of time orbefore, during and after a COVID-19 infection.

Urinary sodium levels fluctuate within a normal range of about 40 toabout 220 mEq/L prior to infection by COVID-19. While not wanting to bebound to theory, it is believed that the onset of a COVID-19 infectionmay result in a decrease in urinary sodium levels. A sudden decrease indaily urinary sodium levels, such as by more than about 5%, more thanabout 10%, more than about 20%, or more than about 35% may indicatesodium retention or an elevation in blood sodium levels.

As such, it is believed a sudden decrease in daily urinary sodiumlevels, such as a decrease of about 10%, about 15%, about 20%, about30%, about 40%, or about 50% when compared to one or more priormeasured, monitored and/or detected urinary sodium levels may indicatethe onset of a COVID-19 infection. Similarly, urinary sodium levels orconcentrations of less than about 40, less than about 30, less thanabout 25, less than about 20, or less than about 15 mEq/L over about a24-hour timeframe may suggest COVID-19 virus binding to ACE2 receptors.In an example, a urine sodium test sample having less than about 20mEq/L may suggest a COVID-19 infection. In another example, less thanabout 40, less than about 30, less than about 25, less than about 20, orless than about 15 mmol urinary sodium per day based on a 24-hour urinecollection may suggest the onset of a COVID-19 infection.

In general, daily monitoring or urinary sodium levels may help toestablish normal urinary sodium levels prior to the onset of a COVID-19infection or illness. While not wanting to be bound to theory, it isbelieved changes from normal urinary sodium to lower urinary sodiumlevels occurs at the start of an COVID-19 infection and this change maybe effective to indicate the start of a COVID-19 infection or illness.Thus, an increase in urinary sodium levels (or urine samples containinghigh levels of sodium) when compared to prior measured, monitored and/ordetected urinary sodium values may correlate to the onset of a COVID-19infection.

Furthermore, while not wanting to be bound to theory, it is believedurinary sodium levels remain lower than normal urinary sodium levels fora period of time during a COVID-19 infection or illness. This timeperiod may vary due to the severity of a COVID-19 infection or illness.In one example, urinary sodium levels remain about 10% lower, about 20%lower, about 30% lower or about 50% lower than previously measured,monitored and/or reported urinary sodium levels for at least 72 hours.In another example, urinary sodium levels remain lower than about 40 mEqper L for at least two days or 48 hours due to the onset or ongoingCOVID infection. In a third example, urinary sodium levels remain lowerthan about 200, about 150, about 100 mEq/L for at least five days due toa COVID infection.

Furthermore, once the infection passes, the body normalizes (recovers orheals) urinary sodium levels increase to normal levels of about 40 toabout 220 mmol per day (or other normal urinary sodium ranges for theindividual) based on a 24-hour collection timeframe. Therefore, dailymeasurement of urinary sodium levels, in a fasted state for example, todetect abnormal decreases in urinary sodium is believed effective todetect the onset, duration and completion of a COVID-19 infection inhealthy, symptomatic and/or asymptomatic individuals.

A COVID-19 infection may also result in an elevated or higher bodytemperature than the normal body temperature of about 97° F. (36.1° C.)to about 99° F. (37.2° C.) in some individuals. As such, periodic and/ordaily monitoring of body temperature is also believed effective todetect the onset, duration and/or completion of a COVID-19 infectionalong with detection, measuring, and/or monitoring one or more ions, oneor more minerals, or any combination thereof when practicing the presentinvention. In one example, an individual body temperature of more thanabout 100.4° F. (38° C.) along with urinary potassium levels of morethan about 20 mEq/L may indicate a COVID-19 infection has started basedon prior measured, monitored and/or detected normal body temperaturesand urinary potassium levels.

A COVID-19 infection may also result in an elevated or higher bloodpressure than the normal blood pressure in some individuals. As such,periodic and/or daily monitoring of body pressure is believed effectiveto detect the onset, duration and/or completion of a COVID-19 infectionalong with detection, measuring, and/or monitoring one or more ions, oneor more minerals, or any combination thereof when practicing the presentinvention. In one example, an individual blood pressure greater than thenormal blood pressure of an individual, such as more than about 110 mmHg to about 144 mm Hg (systolic), about 70 mm Hg to about 81 mm Hg(diastolic), and urinary sodium level of less than about 20 mEq/Lindicates a COVID-19 infection has started based on a prior measurement,such as about a prior 24-hour measurement of normal blood pressure andurinary sodium levels.

Calcium is one of the most abundant minerals in the human body. The bodynormally keeps serum and intracellular calcium levels under tightcontrol through bone resorption and urinary excretion. Furthermore,reference ranges of urinary calcium are dependent on the diet,intestinal absorption, with variations often reported amongst differentlaboratories.

It has been discovered that the onset of a COVID-19 infection may alsobe detected by measuring urinary calcium levels in an individual over anextended period of time, such as over about a 3-day period of time, orabout a 5-day period of time, or about a 7-day period of time, or abouta 10-day period of time, or about a 14-day period of time, or about a21-day period of time, about a 31-day period of time, or before, duringand after a COVID-19 infection.

Typically, urinary calcium levels fluctuate within a normal range ofabout 100 mg/day to about 250 mg/day based on a 24-hour collection timeframe prior to infection by COVID-19. In one example, urinary calciumlevels range from about 15 mmol to about 20 mmol per day, based upon a24-hour collection timeframe.

While not wanting to be bound to theory, it is believed that uponCOVID-19 infection, urinary calcium levels drop significantly, such asmore than about 5%, more than about 10%, more than about 20%, or morethan about 35% as reflected by calcium retention or an elevation inblood calcium, blood serum calcium, and/or serum ionized calcium levels.A decrease in daily urinary calcium levels, such as a decrease of about10%, about 15%, about 20%, about 30%, about 40%, or about 50% whencompared to one or more prior measured, monitored and/or reportedurinary calcium levels may indicate an onset of a COVID-19 infection.Similarly, urinary calcium levels or concentrations of less than about50, less than about 40, less than about 30, less than about 20, or lessthan about 15 mg over a 24-hour timeframe may suggest a COVID-19infection. In an example, a urine calcium sample having about 50 toabout 150 mg calcium per 24-hour timeframe may be due to a COVID-19infection. In another example, less than about 150, less than about 120,less than about 100, less than about 80, or less than about 60 mgcalcium per day based on a 24-hour collection may suggest the onset of aCOVID-19 infection.

In general, daily monitoring of urinary calcium will establish normalurinary calcium levels prior to the onset of a COVID-19 infection. Whilenot wanting to be bound to theory, it is believed changes from normalurinary calcium levels to a decrease in urinary calcium levels (or urinesamples containing lower levels of calcium) when compared to priormeasured, monitored and/or detected urinary calcium values may correlateto the onset of a COVID-19 infection.

Furthermore, while not wanting to be bound to theory, it is believedthat urinary calcium levels remain decreased during a COVID-19 infectionfor a period of time. The time period may vary due to the severity ofthe COVID-19 infection. In one example, urinary calcium levels remainlower for at least about one day. In another example, urinary calciumlevels remain about 10% lower, about 20% lower, about 30% lower or about50% lower than previously measured, monitored and/or detected urinarycalcium levels for about 72 hours during a COVID infection or illnessresulting from the COVID-19 infection. In another example, urinarycalcium levels remain lower than about 150 mg per day for at least about48 hours due to a COVID infection or illness derived from a COVID19infection. In a third example, urinary calcium levels remain lower thanabout 20 mg per day for at least about five days due to a COVID-19infection or illness.

Furthermore, once a COVID-19 infection or illness passes, it is believedcalcium levels normalize (recovers or heals), and blood serum calcium orserum ionized calcium levels return to normal levels for an individual.The effect is an increase in urinary calcium levels to normal levels ofabout 20 to about 250 mg per day for women, about 20 to about 300 mg perday for men, or whatever calcium ranges are considered normal for theindividual, based on a 24-hour urine collection. Daily measurement ofurinary calcium levels, in a fasted state for example, to detectabnormal decreases in urinary calcium is believed effective to detectthe onset, duration and completion of a COVID-19 infection in healthy,symptomatic and/or asymptomatic COVID individuals.

A COVID-19 infection may also result in observing an elevated or higherblood pressure than ranges believed normal for an uninfected individualalong with observation in fluctuations in urinary calcium levels. Assuch, periodic and/or daily monitoring of body pressure is believedeffective to detect the onset, duration and/or completion of a COVID-19infection when performed in combination with detection, measurementand/or quantification of one or more urinary ions, one or more urinaryminerals, or any combination thereof when practicing the presentinvention. In one example, an individual's blood pressure that isgreater than the normal blood pressure range for the individual, such asmore than about 110 mm Hg to about 144 mm Hg (systolic) and about 70 mmHg to about 81 mm Hg (diastolic), along with urinary calcium levels ofless than about 20 mg per day may indicate a COVID-19 infection hasstarted when compared to prior monitored, detected and/or measured bloodpressure and urinary calcium measurements.

It has been discovered that the onset of a COVID-19 infection may alsobe detected by measuring, quantifying and/or monitoring urinary chlorideion levels in an individual. While not wanting to be bound to theory, itis believed that a COVID infection in an individual results in releaseof chloride into the urine. Typically, normal or reference values forurinary chloride levels ranges from about 110 to about 250 mEq per Literper day based on a 24-hour collection timeframe although higher or lowerreference values have been reported based on the amount of wateringested, laboratory protocol, or the like. In one example, normalurinary chloride ranges from about 140 to about 250 mEq per Liter per24-hour timeframe.

A sudden increase in daily urinary chloride levels, such as an increaseof about 10%, about 15%, about 20%, about 30%, about 40%, or about 50%when compared to one or more prior urinary chloride levels may indicatethe onset of a COVID-19 infection. Similarly, urinary chloride levels orconcentrations of more than about 40, more than about 50, more thanabout 75, more than about 100, more than about 125, or more than about200 mEq per liter per 24-hour collection may suggest a COVID-19infection. For example, a urine chloride sample having more than about40 mmol per Liter may suggest a COVID-19 infection.

In general, daily monitoring of urinary chloride levels will establishbaseline and/or normal urinary chloride levels prior to the onset of aCOVID-19 infection. While not wanting to be bound to theory, it isbelieved changes from normal urinary chloride to higher or increasedurinary chloride levels (or urine samples containing high levels ofchloride) when compared to prior monitored, measured, detected, orrecorded urinary chloride values may correlate to the onset of aCOVID-19 infection.

Furthermore, it is believed urinary chloride levels remain elevated fora period of time during a COVID-19 infection. The time period may varydue to the severity the COVID-19 infection or illness. In one example,urinary chloride levels remain about 10% higher, about 20% higher, about30% higher or about 50% higher than previously reported, monitored,and/or measured urinary chloride levels for at least about 24 hours. Inanother example, urinary chloride levels remain higher than about 100mEq per L per 24 hours for at least about 48 hours due to a COVIDinfection or illness. In a third example, urinary chloride levels remainhigher than about 50, about 75, about 100 mmol per Liter for about fivedays due to a COVID infection or illness.

It is also believed that once the COVID-19 infection passes and the bodynormalizes (recovers or heals), urinary chloride levels return to normallevels of about 110 to about 250 mEq per liter per 24 hours (or to theranges are considered normal for the individual). Therefore, dailymeasurement of urinary chloride levels, in a fasted state for example,to detect abnormal increases in urinary chloride is believed effectiveto detect the onset, duration and/or completion of a COVID-19 infection(or illness) in healthy, symptomatic and/or asymptomatic individuals.

As noted above, a COVID-19 infection may result in an elevated or higherbody temperature than the body temperature of an uninfected individual.As such, periodic and/or daily monitoring of body temperature isbelieved effective to detect the onset, duration and/or completion of aCOVID-19 infection when performed along with detecting, measuring,monitoring urinary chloride ion measurements in the present invention.In one example, an individual body temperature of more than about 99° F.along with a urinary chloride level of more than about 40 mEq/L mayindicate a COVID-19 infection has started when compared to prior normalbody temperatures and urinary chloride levels.

It has been discovered that the onset of a COVID-19 infection may alsobe detected by monitoring urinary magnesium ion levels in an individual.While not wanting to be bound to theory, it is believed that a COVIDinfection in an individual results in release of magnesium into theurine. Typically, normal or reference values for urinary magnesiumlevels ranges from about 51 to about 269 mg per 24-hour day based on a24-hour collection timeframe. A sudden increase in daily urinarymagnesium levels, such as an increase of about 10%, about 15%, about20%, about 30%, about 40%, or about 50% when compared to one or moreprior detected, monitored or measured urinary magnesium levels mayindicate the onset of a COVID-19 infection. Similarly, urinary magnesiumlevels or concentrations of more than about 24, more than about 50, morethan about 75, more than about 100, more than about 125, or more thanabout 200 mg per 24-hour collection may suggest a COVID-19 infection orillness.

In general, daily monitoring of urinary magnesium levels may help toestablish normal urinary magnesium levels prior to the onset of aCOVID-19 infection. While not wanting to be bound to theory, it isbelieved changes from normal urinary magnesium levels to higher urinarymagnesium levels (or urine samples containing high levels of magnesium)when compared to prior recorded, monitored, detected or measured urinarymagnesium values may correlate to the onset of a COVID-19 infection.

Furthermore, it is believed urinary magnesium levels remain elevated fora time period during a COVID-19 infection. This time period may vary dueto the severity of a COVID-19 infection or illness. In one example,urinary magnesium levels remain about 10% higher, about 20% higher,about 30% higher or about 50% higher than previously recorded, measured,or monitored urinary magnesium levels for at least about 12 hours. Inanother example, urinary magnesium levels remain higher than about 100mg per 24 hours for at least about 48 hours due to a COVID infection orillness. In a third example, urinary magnesium levels remain higher thanabout 150, about 175, or about 200 mg per 24-hours for at least about 72hours due to a COVID infection or illness.

It is also believed that once the COVID-19 infection passes and the bodynormalizes (recovers or heals), urinary magnesium levels return tonormal levels of about 51 to about 269 per 24 hours (or to ranges thatare considered normal or baseline for the uninfected individual).Therefore, daily measurement of urinary magnesium levels, in a fastedstate for example, may be used to detect abnormal increases in urinarymagnesium and is believed effective to detect the onset, duration andcompletion of a COVID-19 infection in healthy, symptomatic and/orasymptomatic individuals.

The urinary pH for an individual typically ranges from about 4.5 toabout 8.0 in the absence of a COVID-19 infection or illness. In oneexample, the urinary pH of an adult is slightly acidic and ranges fromabout 6.0 to about 7.5. The urinary pH of an individual designated ashaving a COVID-19 infection or illness generally decreases and becomesmore acidic. In an example, the urinary pH of an individual infectedwith COVID-19 ranges from about 7.5 to about 7.0, to about 6.5, to about6.4, to about 6.3, to about 6.2, to about 6.15, to about 6.10, to lessthan about 5.99 during the duration of the COVID-19 infection and/orillness.

In general, daily monitoring of urinary pH levels will help establishnormal or baseline urinary pH (about 4.5 to about 8.0) values prior tothe onset of a COVID-19 infection when practicing the present invention.While not wanting to be bound to theory, it is believed changes fromnormal or baseline urinary pH values to an increase in urinary acidityor reduction in urinary pH may be effective to indicate the start of aCOVID-19 infection when compared to prior measured, monitored,quantified urinary pH values.

It is believed urinary pH levels remain acidic during a COVID-19infection for a period of time. The time period may also vary due to theseverity of a COVID-19 infection or illness. In one example, urinary pHlevels remain about 10% lower, about 20% lower, or about 30% lower thanpreviously detected, recorded, monitored, measured, and/or reportedurinary pH levels for at least about 12 hours. In another example,urinary pH levels remain lower than a pH of about 7.0 for at least about24 hours due to a COVID infection or illness. In a third example,urinary pH levels remain lower than normal or baseline urinary pH valuesfor about 48 hours due to a COVID infection or illness.

Furthermore, once the COVID-19 infection or illness passes and the bodynormalizes (recovers or heals), urinary pH levels are expected to returnto normal or baseline levels of about 6.5 to about 8.0 (or to the normalor baseline range of urinary pH values for the individual prior to aninfection). Therefore, daily measurement of urinary pH levels, in afasted state for example, may be used to detect abnormal increases inurinary pH and is believed effective to detect the onset, duration andcompletion of a COVID-19 infection in healthy, symptomatic and/orasymptomatic individuals.

In general, any suitable thermometer that is effective to measure thebody temperature of an individual may be used to detect, measure,monitor and/or record the body temperature of an individual whenpracticing the present invention. No-touch forehead, body thermometers,and/or other temperature measuring devices are considered suitable foruse when practicing the present invention. For example, a suitabledevice is HEALTH® No-Touch Forehead Thermometer, Digital InfraredThermometer for Adults and Kids, Touchless Baby Thermometer with 3Ultra-Sensitive Sensors, Large LED Display and Gentle Vibration Alert(PT3). Alternatively, one could use a smart phone equipped with a goodthermometer app to monitor, measure, record daily body temperatures whenpracticing the present invention.

In general, any suitable blood pressure device can be used whenpracticing the present invention. An example is the 10 Series® WirelessUpper Arm Blood Pressure Monitor. Alternatively, a smart watch adaptedto measure and record the blood pressure on an individual may also beused when practicing the present invention.

Urinary ions and/or minerals of the present invention, such as sodium,hydrogen, hydroxyl, potassium, calcium, chloride, magnesium,bicarbonate, or the like may be detected, measured, monitored and/orrecorded using one or more ion test kit(s), one or more ion teststrip(s), one or more ion probe(s), one or more ion testing devices, oneor more urine analyzer(s), or any combination of any of these.

In practice, a urine sample is collected and placed inside a samplecontainer. In one example, the urine sample is cleaned prior to testing.In another example, the sample is analyzed as is. In another example,the sample container is outfitted with a semipermeable membrane that iseffective to remove dirt, blood, feces, COVID-19 antigens, COVID-19antigens, any other viral material or the like from the urine sample. Inanother example, the urine sample is collected and placed in contactwith an ion detecting strip that is effective to measure sodium ions. Inanother example, the urine sample is collected and placed in contactwith an ion detecting strip that is effective to measure calcium ions.In another example, the urine sample is placed in contact with achloride detecting strip. In another example, a urine sample iscollected and placed in contact with a strip that is partitioned todetect sodium, potassium, and/or calcium ions. As most ion detectingstrips are based on colorimetric techniques, any resulting color changeresult on the test may be matched to one or more provided color blocksto quantify and/or interpret the results.

Sodium test (dip) strips, such as those that are available fromHOMEHEALTH® (UKI) LTD, Health Mate® Salinity View may also be used todetect the amount of sodium in a urine sample from low (about 0 to about450 mg/dL) to normal (700-1000 mg/dL) to high (about 1200-1600 mg/dL) inabout 60 seconds. Urinary chloride may be detected by urine chloridestrips where urinary chloride is measured by reactive strips based on 24hour samples according to Pannuccio et al (Clin Chem Lab Med 2019 Jul.26; 57(8):1162-1168. doi: 10.1515/cclm-2018-1227). Urinary potassium canalso be detected using the SALIFERT RTKA Potassium Test Kit that isavailable on Amazon.com.

Urine samples may also be analyzed by placing the sample in contact withan ion detecting probe. In one example, the ion detecting probe iseffective to detect, measure, and quantify urinary ions, such as sodium,calcium, potassium, magnesium, chloride, or any combination of these.Measurement and/or quantification may occur through colorimetric,precipitation, flocculation, and/or electrochemical reactions, and theresults through a display in communication with the ion detection probe.

In another example, a urine sample is transferred to a chamber orreceptable for analysis using a urine analyzer. Non exhaustive suitableurine analyzers for determining the pH of a urine sample includeSiemens® 2161 Multistix® 10 SG Reagent Strips for Urinalysis and theFL-401 PRECISION™ Urine Analyzer. The FL-401 PRECISION™ Urine Analyzermeasures and records specific gravity, pH, urinary calcium, creatinine,and other urine analytes in combination with one or more reagent strips,such as the URS-10T Urinalysis Reagent Strips 10 panel.

An example of a device that can detect chloride in a urine sampleincludes the Oakton by Cole-Parmer® Combination Ion-Selective Electrode(ISE), Chloride (CI) that is available from Cole Parmer. Furthermore,this device can be fitted to a pH meter to allow both quantification ofpH and chloride concentrations in a urine sample.

Urinary ions may also be detected using gold nanoparticles (AuNPs) orother nanoparticles modified to give a colorimetric reaction based onionic concentrations in a sample. Gold nanoparticles (AuNPs) have beenwidely used as colorimetric probes for metal ions, anions, smallmolecules, proteins, nucleic acids, and other analytes because of theirunique properties. In one example, a probe solution containing AuNPschange color from red to blue, in the presence of certain ions in amanner that can be observed by the naked eye. AuNPs can also be combinedwith ion detection probes to form ion detection devices that areeffective to determine an ionic concentration in a urine sample andrender results in good agreement with a second ion or mineralconcentration technique, such as atomic absorption spectroscopy (AAS).In another example, calcium ions in a sample may detected using Tween®20-modified gold nanoparticles (GNPs), 2-ME/AuNPs,Cysteine/thioglycolate/triethanolamine-modified GNPs, orCalsequestrin-functionalized GNPs, which are effective to quantifyvarying levels of calcium ions, such as being effective to distinguishbetween normal or baseline calcium levels and lower than normal levelsof calcium ion. In another example, magnesium ions in a sample can bedetected using ACEADD-GNR modified gold nanoparticles.

Furthermore, use of one or more dyes separately or in combination withcolorimetric, electrochemical, precipitation and/or flocculationtechniques known to be effective in detecting, measuring, and/orquantifying one or more ions, one or more minerals, or any combinationsthereof are non-exhaustive examples in practicing the present invention.

Ions in urine samples may also be detected using a smartphone-basedcolorimetric sensor in electronic communication with a machine learning(ML) or deep learning (DL) algorithm that is executed to detect,measure, and/or quantify one or more color changes when practicing thepresent invention. In an example, when one or more ions, or one or moreminerals, or any combinations thereof, are brought into contact with amixture or solution of functionalized gold nanoparticles, the mixture orsolution will change from a first color to a second color. In oneexample, the mixture or solution may change from a red color to a purplecolor in a manner that is proportional to each ion concentration and/orcombined ion concentration in contact with the gold nanoparticles. In asecond example, the mixture may change from a red color to a blue colorin a manner that is proportional to each ion concentration and/orcombined ion concentration in contact with the gold nanoparticles. Thesmartphone camera is turned on and used to capture any color changes inone or more images that may be processed by one or more ML and/or DLalgorithms. The ML and/or DL algorithms have been trained on data tocorrelate color change and/or colors captured or embedded in each imageor pixel to enable prediction of an ionic concentration in a urinesample. In another example, pH, blood pressure and/or body temperaturevalues are used with image and/or color data and fed into ML and/or DLmodels to enable detection, measurement and/or quantification of ionicconcentration.

In another example, ionic concentration can be detected using a devicecomposed of two paper-based elements linked to and in fluidcommunication with each other. For example, one of the two paper-basedelements may be a urine separation unit while the second paper-basedelement may be a colorimetric detection unit. After a urine sample isplaced on or in the separation unit, the separation unit is effective toclean the urine sample and produce a clean urine substantially free ofCOVID-19 antigen, COVID-19 antibodies, dirt, blood, other particulateand/or microparticulates for further testing and analysis. The cleanurine sample is transported to the detection unit, which generallyincludes one or more colorimetric, electrochemical, precipitation,flocculation materials, or suitable ion detecting components that areeffective to detect and/or quantify the ionic levels in the urine sampleand display one or more diagnostic results or colors for analysis.

The present invention may also include a test device for detecting oneor more ions in a urine sample. The test device may contain a chamberthat includes a semipermeable component that is effective to retain (orprevent the passage of) bacteria, virus, parasites, microorganisms,suspended particles, or one more colloids, particles, or suspendedmaterial from a urine sample while allowing the passage or transport ofa filtered urine sample or concentrate containing ions and/or minerals.Some non-exhaustive examples of suitable semipermeable membranes usefulin practicing the present invention include microfiltration membrane,ultrafiltration membranes, nanofiltration membranes, ion permeablemembranes, membranes or materials that are effective to remove COVID-19viral material, antigens and/or antibodies or any combination thereof.The semipermeable membrane is typically effective to produce a cleancatch or clean sample for urine analysis. By clean is meantsubstantially free of dirt, feces, blood particulates, or the like. etc.

The chamber may also include a receiving portion, a concentrate portion,and a channel in fluid communication with the chamber that is effectiveto transfer the filtered urine sample to an ionic detection receptaclethat can detect one or more ions, one or more minerals, or anycombination of any of these. The ion detection receptacle may house anysuitable ion detecting material, such as the above-mentionedfunctionalized nanoparticles, any colorimetric, enzymatic,electrochemical, precipitation, flocculation, or other suitable ionand/or mineral detecting component.

The present invention may include one or more urine test kits containingone or more test strips in communication with or including one or moreion detecting assays embedded therein. Alternatively, the test stripsare in communication with one or more ion detecting assays located on asurface of the test strips. The ion detecting assays may be one or morecolorimetric assays, one or more enzymatic assays, one or moreprecipitation assay, one or more flocculation assays, or any combinationthereof when practicing the present invention.

The ion detecting assays are generally effective to determine theconcentration of or detect the presence of sodium, calcium, potassium,chloride, magnesium, pH, hydrogen ions, hydroxyl ions, bicarbonate,and/or creatinine when practicing the present invention. In one example,a COVID-19 test kit includes a first test strip containing acolorimetric assay or test for sodium ion and a second test stripcontaining a colorimetric assay or test for potassium ion. The test kitgenerally has a potassium ion and/or a sodium ion sensitivity of atleast about 50%, about 60%, about 70%, about 80%, or more than about 85%when practicing the present invention. The test kit may further includea strip for detection of calcium ions, chloride ions, magnesium ions,hydrogen ions, hydroxyl ions, bicarbonate, or any combination thereofand may have a sensitivity of more than about 50%, 60%, 70%, and morethan about 80% when practicing the present invention.

The present invention includes a method of estimating or predicting aCOVID-19 infection by collecting a urine sample from an individualfollowed by performing a first sodium ion urine test of a firstsensitivity with a first test strip at a given time on a urine sample;performing a second ion urine test with a second test strip a secondtime that is at a later time after the first test, and determining aCOVID-19 infection is present when the first test on the first teststrip is positive and the second test on the second strip is positive.In this method, the test strip is effective to detect and/or quantify asodium ion concentration that is less than normal or baseline levels ofurinary sodium ion, a urinary potassium concentration that is more thannormal or baseline levels of urinary potassium, a urinary chlorideconcentration that is more than normal or baseline levels of urinarychloride ions, and/or urinary pH concentrations that are less thannormal or baseline levels of urinary pH for an individual who providedthe urine sample.

The method further includes administering the first test at least about15 minutes, about 30 minutes, about 45 minutes, about 60 minutes, abouttwo hours, about four hours, about 6 hours, 12 hours, about 18 hours,about 24 hours, about 48 hours, or about 72 hours before the secondtest. In one example, the first test result may indicate a positiveinitial COVID-19 infection or illness status that is confirmed by apositive second test result. In another example, the test results arehelpful to establish normal or baseline urinary ions levels. The teststypically have a sensitivity of more than about 50%, about 60%, about70% or more than about 80% when practicing the present invention. Themethod may also include estimating and/or predicting a duration, totalduration, age, and/or length of a COVID-19 infection or illness. Forexample, the levels of detected urinary ions are fed into one or more MLor DL algorithms that are used to estimate the duration, total duration,length, progression, severity, and/or age of COVID-19 infection orillness. By “length” as used herein is meant how long a COVID-19infection or illness has lasted.

In another example, a method of testing for a COVID-19 infectionincludes using a test device that includes at least one assay effectiveto measure an absolute or relative amount of sodium ion, potassium ion,calcium ion, magnesium ion, hydrogen ion, hydroxyl ion, chloride ion, orany combination thereof in a urine sample when practicing the presentinvention. The test device may be in the form of one or more lateralflow test strips, one or more microfluidics-based assays, or anycombination thereof.

In addition, the test device is in communication with a system that iseffective to calculate, estimate, predict, quantify, analyze and/or readone or more urinary ion assay results. The test device may also containa microprocessor, an application-specific integrated circuit, acomputerized control system, or any combination thereof.

The test device may also include a display that is effective to helpcalculate, quantify, predict, estimate, evaluate, analyze and/or displayone or more assay results, one or more outcomes, and/or one or moreoutcomes to a user. The test device may also contain a digital memorydevice programmed with at least one predetermined ion value or ionthreshold for each ion that is being measured. Alternatively, thedigital memory device is programmed with at least one ion value or ionthreshold that represents the difference between two or more urinary ionvalues. In another example, the digital memory device is programed withone or more algorithms that are effective to interpret one or moreurinary ion values, the difference between two or more urinary ionvalues, and/or one or more results, outcomes, statuses produced by thetest device. When the digital memory device is programmed with one ormore algorithms, the digital memory device is in electroniccommunication with the algorithms that are effective to process urinaryion, creatine, pH, body temperature, blood pressure, or mineral data,and produce and/or translate the results into a positive or negative, orunknown COVID-19 infection or illness.

The digital memory device of the test device may also include amicroprocessor, an application-specific integrated circuit, or otherprogrammable computer control system that is programmed with one or morealgorithms that are effective to process, analyze, and/or evaluateurinary ion, mineral, and/or pH data. For example, the algorithm iseffective to process urinary ion, mineral, pH, and/or creatine data bycomparing the detected, measured and/or monitored data withpredetermined thresholds. In another example, the algorithm is effectiveto process urinary ion, mineral, pH and/or creatine data by comparing adifference between two or more values obtained by, stored, and/or madeaccessible to the test device. In another example, the algorithms areeffective to process temperature, blood pressure, urinary ion, pH,mineral and/or creatine data, and to classify or interpret the resultsas positive, negative, or unknown COVID-19 infection or illness status.

The test device is generally effective to interpret at least one ionassay test result and is effective to display at least one test resultto a user. The test device may include one or more light sources toilluminate one or more microfluidics assay detection zones, one or morelateral flow assay detection zones, or any combination thereof alongwith one or more photodetectors that detect light reflected ortransmitted by the detection zones. For example, the detection zonesilluminate a red, yellow or green zone that correlate to positive,unknown or positive negative COVID-19 infection or illness status. Inanother example, the detection zones illuminate a red or green zone thatcorrelate to a positive or negative COVID-19 infection or illnessstatus.

Suitable test devices of the present invention include devices that areeffective to quantify a sodium ion concentration that ranges from lessthan about 20 mEq/L to more than about 220 mEq/L; a potassium ionconcentration that ranges from less than about 20 mEq/L to more thanabout 220 mEq/L; a calcium ion concentration that ranges from less thanabout 50 mg to more than about 150 mg; a chloride ion concentration thatranges from less than about 20 mEq/L to more than about 220 mEq/L; amagnesium ion concentration that ranges from less than about 50 mg tomore than about 300 mg; a creatinine concentration that ranges from lessthan about 100 mg to more than about 3000 mg and/or less than about 10mg/dL to more than about 400 mg/dL per day; a specific gravity of about0.8 to about 1.5; and/or pH values that range from about 1 to about 14.

The test device can be configured to include two more ion assays, suchas for example, assays for sodium ion along with potassium ion or assaysfor calcium ion along with magnesium ion levels in a sample. Thesensitivity of the test device may also have the same degree ofsensitivity for each ion or different sensitivities for each ion.

The assays of the test device may be on separate lateral flow teststrips or separate microfluidic assay flow paths. Alternatively, theassays of the test device may be on a same lateral flow test strip orsame microfluidic assay flow path.

The test device may be programmed with a lower sodium ion threshold andan upper sodium ion threshold. When the test device is programmed with alower sodium ion threshold and an upper sodium threshold, a detected,measured and/or quantified sodium ion value from the test device that islower than the lower sodium ion threshold may indicate a COVID infectionand/or illness is present. Alternatively, if a detected, measured,and/or quantified sodium ion value higher than the upper sodium ionthreshold programmed on the test device may indicate a COVID infectionand/or illness is not present. If the detected, measured, and/ormonitored sodium value result falls between the lower threshold and theupper threshold, the test device may output a classification status asunknown. Furthermore, an unknown COVID-19 infection or illness status ina first test result may subsequently be classified as either a positiveor a negative status after performing a second or additional tests onadditional urinary samples. In another example, if the detected,measured, and/or monitored sodium value result falls between the lowerthreshold and the upper threshold, an indication of a positive ornegative COVID-19 status or result, instead of an unknown status, may beestimated or predicted by evaluating potassium, calcium, hydrogen,hydroxyl, pH and/or chloride ion urinary assay results or data alongwith the sodium value.

The test device may be programmed with a lower potassium ion thresholdand an upper potassium ion threshold. When the test device is programmedwith a lower and an upper potassium ion threshold value, a detected,measured, and/or monitored potassium ion value from the test device thatis lower or below the lower threshold may indicate a COVID-19 infectionand/or illness is not present. Alternatively, a detected, measuredand/or monitored potassium ion value or result that is above or greaterthan the upper potassium ion threshold may indicate a COVID-19 and/orillness is present. If the detected, measured, and/or monitoredpotassium value result falls between the lower threshold and the upperthreshold, the test device may output a classification status asunknown. If the detected, measured, and/or monitored potassium valueresult falls between the lower threshold and the upper threshold, anindication of a positive or negative COVID-19 status or result, insteadof an unknown status, may be estimated or predicted by evaluatingsodium, calcium, hydrogen, hydroxyl, pH and/or chloride ion urinaryassay results or data along with the potassium value.

The test device may also be programmed with a lower chloride ionthreshold and an upper chloride ion threshold. When the test device isprogrammed with a lower and an upper chloride ion threshold value, adetected, measured, and/or monitored chloride ion value from the testdevice that is lower or below the lower threshold may indicate aCOVID-19 infection and/or illness is not present. Alternatively, adetected, measured and/or monitored chloride ion value or result that isabove or greater than the upper chloride ion threshold may indicate aCOVID-19 and/or illness is present. If the detected, measured, and/ormonitored chloride value result falls between the lower threshold andthe upper threshold, the test device may output a classification statusas unknown. If the detected, measured, and/or monitored chloride valueresult falls between the lower threshold and the upper threshold, anindication of a positive or negative COVID-19 status or result, insteadof an unknown status, may be estimated or predicted by evaluatingpotassium, calcium, hydrogen, hydroxyl, pH and/or sodium ion urinaryassay results or data along with the chloride value or by evaluatingadditional urinary samples taken at a later time.

The test device may be programmed with a lower calcium ion threshold andan upper calcium ion threshold. When the test device is programmed witha lower and an upper calcium ion threshold value, a detected, measured,and/or monitored calcium ion value from the test device that is lower orbelow the lower threshold may indicate a COVID-19 infection and/orillness is not present. Alternatively, a detected, measured and/ormonitored chloride ion value or result that is above or greater than theupper calcium ion threshold may indicate a COVID-19 and/or illness ispresent.

If the detected, measured, and/or monitored calcium value result fallsbetween the lower threshold and the upper threshold, the test device mayoutput a classification status as unknown. If the detected, measured,and/or monitored calcium value result falls between the lower thresholdand the upper threshold, an indication of a positive or negativeCOVID-19 status or result, instead of an unknown status, may beestimated or predicted by evaluating potassium, sodium, hydrogen,hydroxyl, pH and/or chloride ion urinary assay results or data alongwith the calcium value. If the detected, measured, and/or monitoredcalcium value or result is between the lower threshold and the upperthreshold, this may indicate that a COVID infection is or is notpresent, and may result in the test device outputting an unknownCOVID-19 infection or illness result in the present invention. If thedetected, measured, and/or monitored calcium value result falls betweenthe lower threshold and the upper threshold, an indication of a positiveor negative COVID-19 status or result may be calculated by incorporatingsodium, chloride, hydrogen, hydroxyl, pH and/or potassium ion assayresults or data, and estimating or predicting COVID-19 infection orillness status from the combination of this data or by evaluatingadditional urinary samples taken at a later time.

The test device may be programmed with a lower magnesium ion thresholdand an upper magnesium ion threshold. When the test device is programmedwith a lower and an upper magnesium ion threshold value, a detected,measured, and/or monitored magnesium ion value from the test device thatis lower or below the lower threshold may indicate a COVID-19 infectionand/or illness is not present. Alternatively, a detected, measuredand/or monitored magnesium ion value or result that is above or greaterthan the upper magnesium ion threshold may indicate a COVID-19 and/orillness is present. If the detected, measured, and/or monitoredmagnesium value result falls between the lower threshold and the upperthreshold, the test device may output a classification status asunknown. If the detected, measured, and/or monitored magnesium valueresult falls between the lower threshold and the upper threshold, anindication of a positive or negative COVID-19 status or result, insteadof an unknown status, may be estimated or predicted by evaluatingpotassium, calcium, hydrogen, hydroxyl, pH and/or chloride ion urinaryassay results or data along with the magnesium value, or by evaluatingadditional urinary samples taken at a later time.

The test device may be adapted and configured to display an approximateCOVID-19 infection and/or illness age, duration, total duration, length,progress, and/or severity calculated for a urine sample or individual.The age, duration, total duration, length, progress, and/or severity ofthe COVID-19 infection and/or illness may be outputted in intervals ofminutes, hours, days, weeks, or months. For example, the duration outputmay be 24 hours. In another example, the length output might be twoweeks.

The test device may also include a control function to indicate if thedevice is functionally correctly or has functioned correctly. The testdevice may be a point-of-care device or a test device that is disposedof after a single use.

The test device of the present invention may include a moistureimpermeable housing that is effective to house one or more components ofthe test device, and a sample application zone located on a sampleapplication member that extends from the moisture impermeable housing toallow a urine sample to be applied or placed in contact with the testdevice. A common sample application zone in fluid communication with twoor more distinct flow paths, such that each distinct flow path containsor houses a different analyte (ion) assay may also be present in thetest device. The test device is generally effective to detect, measure,monitor, record and/or display an absolute or relative amount, level orconcentration of one or more calcium ions, chloride ions, sodium ions,magnesium ions, potassium ions, creatinine, hydrogen ions, hydroxylions, or any ionic combination thereof.

The test device may include a disposable visually-reading devicecombined with a separate durable assay reading device, such that theseparate durable assay reading device comprises a camera, a smart phoneor other digital hand-held reading device.

As noted, urinary ionic and/or mineral levels or concentrations may alsobe monitored at specified time intervals for a specific length of timein an amount that is sufficient to establish normal or baseline valuesto help analyze or interpret test device data. For example, dailysodium, potassium, chloride, blood pressure, pH and/or temperaturevalues may be recorded and prove helpful in establishing baselinevalues. In another example, urinary sodium, potassium, chloride, bloodpressure, pH and/or temperature values may be monitored or recordedevery 15, 30, 45, 60, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, or48 hours in order collect data suitable for training one or morealgorithms to estimate or predict COVID-19 infection and/or illnessresult or status. In another example, daily urinary sodium, pHpotassium, calcium, and chloride levels along with blood pressure may bemonitored for at least 3 days and used to estimate or predict a COVID-19infection. In another example, daily body temperature, blood pressure,and urinary potassium, chloride, pH and creatinine values are measured,recorded for at least seven days and used to determine a COVID-19infection status. In another example, urinary sodium, potassium,calcium, chloride and magnesium levels, urinary pH, blood pressure andcreatinine data are measured, recorded for at least one time and may beused to estimate or predict a COVID-19 infection.

In general, one or more artificial intelligence algorithms, such as oneor more ML algorithms, one or more DL algorithms, or any combination ofthese, can be trained using sodium, potassium, chloride, calcium, and/ormagnesium data, pH, creatinine, blood pressure, body temperature and/orspecific gravity data to create one more ML and/or DL models effectiveto estimate or predict COVID-19 infection or illness status, duration,total duration, length, severity, and/or age when practicing the presentinvention.

For example, a dataset from one or more individuals based on a timeframeof one or more days, similar to that which is presented in TABLE 1A and1B, can be used to train an ML classifier and/or regressor in order toestimate or predict COVID-19 infection or illness status as well asinfection length, age, duration and/or total duration in the presentinvention.

The present invention may typically include running or executing one ormore ML and/or DL models that have been trained with ionic and/ormineral data and are effective to analyze, interpret and/or enableestimation and/or prediction of COVID-19 infection or and/or illnessstatus, age, duration, severity and/or total duration.

In an example, data from at least 1 day, 3 days, 5 days, 10 days, 15days, 20 days, or 31 days can be used as normal or baseline urinaryvalues to train a ML model, such as a gradient boosting classifier. Inanother example, data from at least 1 hours, 2 hours, 4 hours, 6 hours,12 hours, 24 hours, 3 days, 5 days, 7 days, 18 days, or 15 days of aCOVID-infection can also be used to train an ML model, such as agradient bosting classifier.

While the data in Table 1A, 1B and 2 are presented in different tables,both “normal” and “COVID-19 infection” data can be combined into onedataset and used for training, testing, validation, estimation, andprediction of COVID-19 infection or illness status. Table 3 is anexample of a dataset suitable for training one or more ML and/or DLmodels.

ML algorithms generally include logistic regression, linear regression,naïve bayes classifier, random forest, support vector machine, decisiontree, gradient boosting regressor, gradient boosting classifier, or thelike. Data is typically split into training and test samples prior tofeeding (inputting) into one or more ML and/or DL algorithms.

Alternatively, a deep learning neural network known as a convolutionalneural network, or ConvNet, can be used to tell how much ionconcentration, such as how much sodium, potassium, chloride, etc., maybe present in a urine sample based on the one or more pixels captured bythe smartphone camera. Additional examples of DL models includerecurrent neural networks, CNN, LSTM and/or combinations thereof.

In an example, when urinary potassium and chloride levels greater thanor higher than normal or baseline urinary values, and urinary pH valueslower than normal or baseline urinary pH values are inputted into one ormore ML models of the present invention that are trained to predictCOVID-19 infection or illness status, a positive COVID-19 infectionstatus or illness was predicted, displayed, and recorded. In anotherexample, a positive COVID-19 infection status or illness may beestimated or predicted when urinary sodium, potassium and chloridelevels greater than normal urinary values, and urinary pH values lowerthan normal urinary pH values are inputted into one or more ML models ofthe present invention that are trained to predict a COVID-19 infectionor illness. In another example, a positive COVID-19 infection status orillness may be estimated or predicted when urinary calcium, potassiumand chloride levels greater than normal urinary values, and urinary pHvalues lower than normal urinary pH values are inputted into one or moreML models of the present invention that are trained to predict aCOVID-19 infection or illness. In another example, a positive COVID-19status or illness may be predicted when urinary magnesium, potassium andchloride levels greater than normal urinary values, and urinary pHvalues lower than normal urinary pH values are fed into one or more MLmodels of the present invention that are trained to predict a COVID-19infection or illness.

A negative COVID-19 infection status or illness may be predicted whenurinary potassium and chloride levels lesser than or within normalurinary values, and normal urinary pH values are fed into one or more MLmodels of the present invention that are trained to predict a COVID-19infection or illness. A negative COVID-19 infection status or illnessmay also be predicted when urinary sodium, potassium, and chloridelevels lesser than or within normal urinary values, and normal urinarypH values are inputted into one or more ML models of the presentinvention that are trained to predict a COVID-19 infection or illness. Anegative COVID-19 infection status or illness may also be predicted whenurinary calcium, potassium, and chloride levels lesser than or withinnormal urinary values, and normal urinary pH values are fed into one ormore ML models of the present invention that are trained to predict aCOVID-19 infection or illness.

A first unknown COVID-19 infection status or illness may be predictedwhen urinary sodium, potassium and chloride levels lesser than or withinnormal urinary values, and normal urinary pH values are fed into one ormore ML models of the present invention that are trained to predict aCOVID-19 infection or illness. A second negative COVID-19 infection orillness status may be predicted should second or additional urinary testresults with similar urinary sodium, potassium and chloride levelslesser than or within normal urinary values along with normal urinary pHvalues are evaluated using one or more ML models of the presentinvention that are trained to predict a COVID-19 infection or illness.

A first unknown COVID-19 infection status or illness may be predictedwhen normal urinary pH values, urinary potassium, and chloride levelsgreater than normal urinary values, and urinary sodium values that areless than normal urinary sodium values are evaluated by one or more MLmodels of the present invention that are trained to predict a COVID-19infection or illness. A second positive COVID-19 infection or illnessstatus may be predicted should second or additional urinary test resultscollected within or after a 2-hour timeframe based on similar normalurinary pH values, urinary potassium, and chloride levels greater thannormal urinary values, and urinary sodium values that are less thannormal urinary sodium values are evaluated using the ML models of thepresent invention that are trained to predict a COVID-19 infection orillness.

What is claimed is:
 1. A method of producing a COVID-19 result status ofa subject utilizing a urine sample, the method comprising: providing afirst ion detecting component for measuring sodium ions; providing asecond ion detecting component for measuring potassium ions; contactingthe urine sample with the first ion detecting component to determine ameasured sodium ion value; contacting the urine sample with the secondion detecting component to determine a measured potassium ion value;comparing the measured sodium ion value to a baseline sodium ion valuecollected at least 12 hours before the measured sodium ion value;comparing the measured potassium ion value to a baseline potassium ionvalue collected at least 12 hours before the measured potassium ionvalue; and wherein a positive COVID result status occurs when themeasured sodium ion value is lower than the baseline sodium ion valueand the measured potassium ion value is higher than the baselinepotassium ion value in the urine sample.
 2. The method of claim 1wherein classifying the urine sample comprises executing at least onealgorithm on an analyzing component in electronic communication with thefirst ion detecting component and the second ion detecting component. 3.The method of claim 1 further comprising filtering the urine sampleusing a semipermeable membrane.
 4. The method of claim 2 furthercomprising storing the measured sodium ion value or measured potassiumion value on a storage component of the analyzing component.
 5. Themethod of claim 1 wherein the first ion detecting component and thesecond ion detecting component are located on an ion detecting strip. 6.A method of producing a COVID-19 infection status in a subject utilizinga urine sample, the method comprising: contacting the urine sample withan ion detecting probe; detecting a potassium ion level with the iondetecting probe; detecting a chloride ion level with the ion detectingprobe; and wherein a COVID-19 positive status occurs when the detectedpotassium ion level is higher than a threshold potassium level collectedat least 12 hours before the measured potassium ion value, and thedetected chloride ion level is higher than a threshold chloride ionlevel collected at least 12 hours before the measured chloride ionvalue.
 7. The method of claim 6 wherein the COVID-19 positive statusoccurs when the measured pH is lower than the baseline pH concentration.8. A method of producing a COVID-19 infection result status of a subjectutilizing a urine sample, the method comprising: contacting the urinesample with an ion detecting probe; measuring a sodium ion level and apotassium ion level with the ion detecting probe; and, algorithmicallyproducing the urine sample COVID-19 status by comparing the measuredsodium ion level and the measured potassium ion level to respectivebaseline sodium ion concentration and potassium ion concentrationscollected at least 15 minutes before the measured sodium ion level andpotassium ion level.
 9. The method of claim 8 wherein a positiveCOVID-19 status is algorithmically produced when the measured sodium ionlevel is lower than the baseline sodium ion concentration and themeasured potassium ion level is higher than the baseline potassiumconcentration.
 10. The method of claim 8 wherein algorithmicallyproducing the urine sample COVID-19 status comprises classifying thedifference between the measured sodium ion level and the baseline sodiumconcentration and the difference between the measured potassium ionlevel and the baseline potassium ion concentration.
 11. The method ofclaim 8 wherein algorithmically producing the urine sample COVID-19status comprises execution of at least one algorithm based on at leastone past sodium ion and potassium ion concentrations.
 12. The method ofclaim 1 wherein the first ion detecting component and the second iondetecting component are located on separate ion detecting strips. 13.The method of claim 1 wherein the first ion detecting component and thesecond ion detecting component are located on an ion detecting probe.14. The method of claim 1 wherein the first ion detecting component islocated on a first ion detecting probe and the second ion detectingcomponent is located on a second ion detecting probe.
 15. The method ofclaim 1 wherein the first ion detecting component includes goldnanoparticles.
 16. The method of claim 8 wherein a negative COVID-19result status in the urine sample is produced when the measured sodiumion level is equal to the baseline sodium ion concentration and themeasured potassium ion level is equal to the baseline potassiumconcentration.
 17. The method of claim 8 wherein an unknown COVID-19result status in the urine sample is produced when the measured sodiumion level is equal to or higher than the baseline sodium ionconcentration and the measured potassium ion level is equal to or lowerthan the baseline potassium concentration.